生化学と薬理学: オープンアクセス
オープンアクセス

概要

Synthesis and Evaluation of Ornithine Decarboxylase Inhibitors with Oxime Moiety and MCF-7 Breast Cancer Cells

Hyunshun Shin, Heather Whitehead, Xian Zhou, Karl L Banta, Juliet V Spencer, Myung K Cho and Sung-Kun Kim

Cell proliferation can be regulated by small, aliphatic polyamines, and it is suggested that tumor tissues have significantly higher polyamine levels than surrounding tissues. The major biologically active polyamines present in mammalian cells are putrescine, spermidine, and spermine. The Ornithine Decarboxylase (ODC) catalyzes the decarboxylation of ornithine to produce putrescine which is precursor of polyamine synthesis. We report here the synthesis of 2-Amino-5-(Hydroxyimino) Pentanoic Acid (AHPA), based on the substrate of ODC, L-ornithine, derivatized with oxime functionality. In molecular docking studies, the E-isomer AHPA binds to ODC more favorably than does the
Z-isomer. In addition, the growth of MCF-7 (Michigan Cancer Foundation–7) breast cancer cells in the presence of AHPA was significantly reduced. These results implicate that AHPA a potentialt can be explored as a potential of cancer chemotherapy.